In this retrospective study, we observed a median 2.0 day decrease in time from surgery to discharge, a significantly lower postoperative complication rate (e.g., atelectasis), and a similar mortality over 1 year after the surgery when reversed with sugammadex compared to pyridostigmine. Moreover, sugammadex was the only intraoperative predictor associated with reduced LOS.
Hospital LOS was decreased, as was the incidence of adverse postoperative outcomes (e.g., atelectasis) in patients reversed with sugammadex for NMB, in line with previous studies that reported that the use of sugammadex is associated with 20% shorter LOS with reduced postoperative adverse outcomes after major abdominal surgery and is associated with a 0.6 day shorter hospital LOS and a lower postoperative complication rate after laparoscopic gastric cancer surgery. Residual neuromuscular paralysis occurs in approximately 20–60% of surgical patients and is associated with an increased incidence of PPCs (e.g., hypoxemia and atelectasis). On the other hand, sugammadex has been shown to reduce the incidence of residual paralysis upon arrival in the PACU compared to other classic NMB reversal agents. Therefore, sugammadex may decrease hospital LOS through its improved muscle relaxant reversal, leading to a reduction in PPCs and early patient discharge.
By contrast, Ledowski et al. observed that overall hospital LOS after surgery did not differ between patients treated with sugammadex or acetylcholinesterase inhibitors; the cause of this discrepancy remains unclear. It has been shown that postoperative residual NMB and associated adverse PPCs are more common in elderly patients than in younger patients. Moreover, thoracic and abdominal procedures that reduce lung volume are associated with increased risk of developing atelectasis and postoperative complications. Ledowski et al. studied relatively young patients (mean age ~ 50 years) who underwent surgical procedures including orthopedic, plastic, general, and others, whereas we studied elderly patients (mean age ~ 66 years) who underwent open lung surgery. Thus, different ages of surgical populations and type of surgery may be responsible for differences between the studies. Indeed, Ledowski et al. demonstrated that NMB reversal with sugammadex significantly improves postoperative pulmonary outcomes compared to neostigmine, particularly in elderly patients.
It has previously been reported that poorly controlled acute postoperative pain is a risk factor associated with respiratory complications, and that postoperative pain may lead to the development of atelectasis because it can interfere with the normal activity of respiratory muscles and forced respiratory effort. On the other hand, other studies have shown that epidural analgesia provides better postoperative pain control than systemic opioid administration in abdominal or open thoracotomy surgery[29, 30]. In the present study, epidural patient-controlled analgesia was used less commonly in patients reversed with sugammadex than those reversed with pyridostigmine. Nevertheless, the sugammadex group was associated with a lower incidence of atelectasis. Thus, sugammadex restores the function of the respiratory muscles more quickly and completely and reduces the incidence of PPCs, such as atelectasis, although the severity of pain is greater in the sugammadex group than in the pyridostigmine group. These findings are in accordance with those of a recent study that showed that patients reversed with sugammadex had fewer postoperative complications and a shorter LOS despite more severe postoperative pain compared to those with neostigmine in patients who had undergone laparoscopic gastric cancer surgery.
Several studies have reviewed patients undergoing pulmonary resection for lung cancer and identified risk factors for prolonged hospital LOS[1, 20, 28, 31–34]. Some risk factors identified previously include older age[20, 32, 33], male sex, ASA physical status score[20, 32], insulin-dependent diabetes, renal dysfunction, percentage predicted FEV1[20, 33], surgeon, smoking, COPD, and postoperative complications (e.g., pneumonia[32, 33], unplanned reintubation[32, 34], or prolonged ventilation[32, 34]). In this study, we confirmed the important risk factors for morbidity and prolonged LOS after lung resection (Tables 4,5). Interestingly, we found that sugammadex (vs. pyridostigmine) was protective against prolonged hospital LOS, supporting a benefit with respect to patient outcomes and associated hospital costs. In fact, the use of sugammadex is becoming increasingly common for NMB reversal, particularly in the elderly, with the advantage that it can reverse profound NMB, although reversal agent options are currently limited by price.
Overall survival 1 year after surgery did not differ between the two reversal agents (Fig. 3). Death after lung cancer surgery may be attributable to surgery-related major complications and to cancer progression. Although sugammadex decreases the incidence of PPCs and shortened hospital LOS in the present study, this agent is unlikely to significantly reduce surgery-related major complications. In addition, we found that once a patient reached a medically stable state and was discharged, the mortality after 1 year was not different across the type of reversal agent, suggesting that an advantage for sugammadex does not extend to the long term.
This study had several limitations. First, it was a small, single center, retrospective study. Not all covariates were controlled, although the demographics and clinical characteristics were balanced by propensity score matching. Second, some fundamental intra- or postoperative covariates associated with respiratory complications were not collected. The degree of pain after surgery is considered an important factor associated with respiratory complications. The severity of pain and opioid consumption were not assessed in this study. In addition, the total dose of neuromuscular blocking agent administered and depth of NMB at the time of reversal were not included in our analyses. Use of single or repeated doses and depth of NMB at the time of reversal are important factors that affect recovery after NMB. Third, diagnosis of atelectasis was entirely dependent on plain chest radiographs, although only relatively obvious cases of atelectasis seen on plain radiography were included. However, this technique for the diagnosis of postoperative lung collapse is less sensitive than computed tomography, which was not routinely performed after open lobectomy in our hospital. Finally, the type of surgical approach and the extent of surgery are strongly related to patient outcomes. However, the cohorts analyzed were a highly selective group that underwent open lobectomy for lung cancer.